944
E. T. MCBEE,H. B. HASS,R. M. THOMAS, W. G. TOLAND, JR., AND A. TRUCHAN Vol. 69
12-(2'-Ethoxyethyl) -9-amino-1,2,3,4,9,10,11,12-octa- alcohol was largely removed and the organic material exhydrophenanthrene, V.-In the best of several attempts, tracted t o yield 1.63 g. of a substance which was much 9.08 g. of oxime, purified by extraction from petroleum more fluid than the starting material. On triturating ether solution with Claisen alkali and precipitation with with Skellysolve B 0.37 g. remained undissolved. Analyacid, in 200 cc. of pure anhydrous butyl alcohol at 80" was sis showed it to contain 6% of bromine so i t was not furtreated with 14 g. of sodium. The mixture rapidly heated ther studied. On treatment of the Skellysolve B soluble up enough to melt the sodium and was shaken occasionally fraction with dry hydrogen chloride, a crude hydrochloride to break up the molten globules of sodium. At the end fraction was obtained which was only partially soluble in additional heat was required to complete the reaction. water. The water insoluble fraction was discarded after The crude amine thus obtained was purified by dissolving preliminary examination and the soluble fraction was in dry petroleum ether to which dry hydrogen chloride made alkaline. The amine thus obtained was vacuum was added. The precipitated hydrochloride was collected, distilled (bath temperature, 180", pressure 0.5 mni.) to washed, and treated with alkali. There was thus ob- yield 25 mg. of almost colorless, rather fluid product. tained 5.5 g. (64%) of faintly yellow viscous amine, n8D AnuLa Calcd. for ClaHzlN: C, 84.5; H, 9.3; N, 6.2. 1.5518, which distillei at 0.5 mm. when the bath tempera- Found: C, 84.0; H, 9.4; N, 5.8. More of a similar product was ture was about 190 A small amount of solid chloroplatinate was made and obtained in 21 % yield from the non-crystalline material analyzed for platinum. remaining after the separation of the crystalline oxime Anal. Calcd. for C32H44N2PtC16: Pt, 22.6. Found: acetate described above. A n d a Calcd. for C18H2rON: C, 79.1; H, 10.0; N, Pt, 22.2. A Van Slyke amino-nitrogen determinations showed that 5.1. Found: C, 78.1, 78.4; H,9.8, 9.9; N, 4.9,4.9. The neutral fraction remaining after removal of the 56.2% of this product was primary (undesired) amine, amine hydrochloride yielded a small amount of an oily probably 9-amino-12-vinyl-1,2,3,4,9,10,11,12-octahydroliquid which distilled a,t 0.5 mm. when the bath tem- phenanthrene. The remainder was probably the desired This fraction was larger when secondary amine, VII, but further work must be done beperature was about 190 oxime not purified by the Claisen alkali treatment was fore this synthesis is firmly established. 12-(2 '-Ethoxyethyl) -9-keto-l0-oximino-l,2,3,4,9,10,11,used. Treatment with methylmagnesium iodide showed that this substance contained an active hydrogen, and on 12-octahydrophenanthrene,VII1.-The ketone, IV, was analysis, figures consistent with the formulation as 12-(2'- nitrosated with i-amyl nitrite and potassium ethoxide16 ethoxyethyl) 9 hydroxy - 1,2,3,4,9,10,11,12 - octahy- to yield 62% of a yellow-orange oil soluble in Claisen alkali. This material could not be vacuum distilled or crystallized droDhenanthrene were obtained. but gave the expected analytical figures for VI11 after Anal: Calcd. for C18H2604: C, 78.8; H , 9.6. Found: partial purification by chromatographic adsorption over C, 79.1, 78.7: 13, 9.1, 8.9. a mixture of 5 parts calcium silicate (Silene, Pittsburgh ~1,3,4;9,10,10a~Hexahydro-9,4a(2) -iminoethanophenanPlate Glass Co.) and 1part celite No. 535 (Johns Manville threne, VI1.-On refluxing a solution of 3.35 g. of the above Co.)had removed a dark colored impurity. amine in 60 cc. of 48% hydrobromic acid, an insoluble comAnal.@ Calcd. for Cl8HBa03N: C, 71.7; H, 7.7; K, pound separated. On extraction, washing, and removal of solvent, 3.25 g. of a brittle resin-like substance was ob- 4.6. Found: C, 71.7; H,7.9; N,4.7. tained. Since this product could not be distilled or crysSummary tallized readily, i t was immediately subjected to cyclization attempts. An analysis of the crude material is given. Steps in the attempted synthesis of 1,3,4,9,10,A n d o Calcd. for CleHzzNBr: C, 62.3; H, 7.2; N, lOa-hexahydro-9,4a(2)-iminoethanophenanthrene 4.5; Br, 25.9. Found: C, 56.2; H, 6.7; N, 3.8; Br, are described. 26.2. In the best of several attempts a t cyclization, 1.88 g. of 283 (1928); J. von Brauo and K. Schwarz, i b i d . , 481, 56 (1930) bromoamine in 50 cc. of 95% ethyl alcohol was added to V. Prelog, i b i d . , 545, 229 (1940). 500 cc. of lo%, sodium hydroxide containing 200 cc. of (15) A. Pictet and A. Gams, Ber., 42, 2943 (1909); L. Claisen ethyl alcohol.1* After keeping at 60" for three days, the ibid., 20, 655 (1887). ____(14) Compare J. von Braun, W. Haensel and F. Zobel, A n n . , 464, COLUMBUS 10, OHIO RECEIVEDDECEMBER 16, 1946
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[CONTRIBUTION FROM THE DEPARTMENT OF CHEMISTRY AND THE PURDUE RESEARCH FOUNDATION, PURDUE
UNIVERSITY]
Fluorinated Derivatives of Propane BY
E.T.MCBEE,H. B. HASS,R. M. THO MAS,^ W. G. TOLAND, JFL,~ AND A. TRUCHAN
This work is an extension of the research undertaken for the purpose of synthesizing fluorine-containing compounds for pharmacological tests. The synthesis of certain fluor0 derivatives of propane hits been described in a previous paper.4 (1) The major portion of this paper is taken from the Ph. D. Thesis submitted to the faculty of Purdue University by R. M. Thomas in 1942. (2) Present address: Firestone Tire and Rubber Co., Akron, Ohio. (3) Present address: California Research Corporation, Richmond, California. and N. Elmore, THIS (4) E. T. McBee, A. L. Henne, R. B. HUES J O U ~ N A L ,08, aate (1940). .
The investigation has now been extended to include additional derivatives of propane. The fluorination of CC13CH2CH3with antimony fluoride gives a 5 1 0 % yield of CF~CHZCH~.~ Three new syntheses for the preparation of l,l,ltrifluoropropane have been developed, namely, fluorination of CC13CH2CH8, C C ~ F C K C H ~and 1,l-dichloro-cyclopropanewith hydrogen fluoride. These reactions also yielded CClFzCHCH3 and CCI~FCH~CHB. This same fluorination procedure (5) A, L, Henna and A. M. Whaley, ibid., 64, 1157-1160 (1942).
April, 1947
FLUORINATED DERIVATIVES OF
PROPANE
945
was used to prepare bromofluoropropanes. Flu- of 750 ml. capacity which was tested a t 340 atm. (5000 in.). These autoclaves, equipped with removable orination of CH2BrCBr2CH2Bryielded CH2BrCF2- lb./sq. heads, were mounted within a shelter of 1/2-inchiron plate. CH2Br and fluorination of CBrCI2CHBrCH3gave Only valve handles, gages, and exhaust lines were exposed CF3CHBrCH3. as the principal product with a in the operation. When hydrogen fluoride alone was the fluorinating agent, small amount of CC1F2CHBrCH3. Treatment of starting material was poured into the autoclave and the CHBrC1CHBrCH3 in the same manner produced head fastened in place. Hydrogen fluoride was introthree new compounds, CHC1FCHBrCH3, CHF2- duced into the autoclave from a 600-ml. iron container, CHBrCH3,and CHClFCHFCH3, which were iden- fitted with a brass needle valve and connected with the tified by boiling point analogies and halogen fluorination equipment, the transfer being facilitated by heating the cylinder. After addition of hydrogen fluoanalyses. ride, the autoclave was heated; when reaction was comThermal and photochemical chlorination of the plete, gaseous products were discharged into 6 N sodium above chlorofluoropropanes yielded new chlorin- hydroxide equivalent in quantity to the hydrogen fluoride ated derivatives of interest as anesthetics. One charged. Organic material which did not condense in the passed through a drying tower into a receiver dichlorodifluoropropane obtained by chlorination ascrubber t Dry-Ice temperature. of CCIF2CH2CH3was identified as CCIF2CHClWhen mercury(I1) fluoride was used as fluorinating CH3 by agreement of its physical properties with agent, it was prepared in situ by reaction of hydrogen those of the CClF2CHClCH3 obtained from re- fluoride with red mercury(I1) oxidee9 Due to the highly exothermic nature of the reaction, the autoclave was first action between CCl3CHClCH3, mercury(I1) oxide, cooled to -70" with a Dry-Ice and trichloroethylene bath, and hydrogen fluoride. The other dichlorodifluoro- material to be fluorinated then added. Hydrogen fluopropane was assigned the formula CC1F2CH2CH2- ride was added directly from a small cylinder. Mercury C1, since only two isomeric dichlorodifluoropro- (11) oxide was then added portionwise with stirring. After addition of reagents was complete, the autoclave was panes are possible from the chlorination of CClF2- assembled and heating begun. Reaction products were CH2CH3and since the boiling point was in agree- discharged as before. ment with the value predicted from known cornResidues in the alkali wash bottle were steam-distilled; all products were combined, dried, and rectified in a suitpounds. Three isomeric trichlorodifluoropropanes are able column, a low-temperature column being used for of compounds boiling below room temperature possible from chlorination of CCIF2CH2CH3, separation and a Lecky-Ewe11 column (24 inches long X '/?-inch namely, CCIF2CC12CH3, CCIF2CHClCH2C1, and diameter) for separation of higher-boiling liquids. Fluorination of CC13CH2CH3.-Three moles of CC13CCIF2CH2CHC12. Only the last was isolated from the chlorination of CClF2CH2CH3, but the others CH2CH3,prepared by the method of Levine and Cass,lO 16 moles of anhydrous hydrogen fluoride were heated may have been present in traces. Identification and in the Monel autoclave a t 100-119" for fourteen hours. of CClF2CHzCHC12 was established by further Maximum uressure of about 82 atni. 11200 lb./sa. in.) chlorination to CClF2CH2CC13 and conversion of was obseried. Rectification of the reaction ' p;oduA the latter compound to CF3CH2CF3,6 a known gave 0.38 mole of CC12FCH2CH3, 2.0 moles of CClF2CH2CH3,and 0.34 mole of CF3CHzCH3. Yields were, resubstance. spectively, 12.7, 67.5 and 11.3%. Two trichlorodifluoropropanes were formed by Fluorination of CCl2=CHCHs.-The Monel autoclave the vapor phase photochemical chlorination of was charged with 2 moles of CClz=CHCH3 and 15 moles One of these com- of hydrogen fluoride. After charging, the autoclave CClFzCHClCH3 a t 84-88'. and contents were heated to 90-100' for seventy-two pounds boiled c ~ ~
CFs
2
3
c1
c1
c1
4
CFI 5
6
c1 &FJ
7
c1
= F3c--~-cF, 8
Experimental Preparation of Starting Materials 2- and 4-Chloro-(trifluoromethyl)-benzenes.-These compounds were prepared by the fluorination of commercially available 2- and 4-chloro-(trichloromethyl)-benzenes. The fluorination was carried out a t room temperature in iron equipment using anhydrous hydrogen fluoride in the presence of a small quantity of antimony(V) chloride as the fluorinating agent. 2-Chloro-(trifluoromethyl)-benzene (b. p. 148-150" (745)) was obtained in 85y0 yield; 4-chloro-(trifluoromethyl) -benzene (b. p. 135-136' (745)) was obtained in 91% yield. 3-Chloro-(trifluoromethyl)-benzene .-This compound (b. p. 135-136' (745)) was prepared according to the method of Holt and Daudta by the chlorination, in glass (6) Holt and Daudt (to du Pout). U. S. Patent 2,174,513, Oct. 3,
1939.
